1. Field of the Invention
The present invention relates to recombinant neuraminidase and uses thereof, particularly to recombinant neuraminidase capable of being used as universal influenza vaccine and uses thereof.
2. Description of the Prior Art
Members of the Orthomyxoviridae family, influenza A viruses are enveloped viruses containing a single strand, 8-segment negative sense RNA genome typically encoding 11-12 viral proteins. Influenza A virus subtypes have been classified based on the antigenic properties of hemagglutinin (HA) and neuraminidase (NA) glycoproteins, respectively designated as H1-H16 and N1-N9. One recent report describes H17N10 and H18N11 identified from fruit bats. According to phylogenetic analyses, N1-N9 can be classified as belonging to group 1 (including N1, N4, N5 and N8) or group 2 (including N2, N3, N6, N7 and N9). To date, only N1, N2 and N9 subtypes are known to trigger human epidemics.
NA, an enzymatic protein with a tetrameric complex structure, is capable of cleaving sialic acid linkages on cell surfaces, thereby facilitating viral release from infected cells. NA also contributes to viral transmission and infection by destroying decoy receptors on cilia, mucins, and cellular glycocalyx. NA immunogenicity was first observed in human subjects immunized with a NA-specific inactivated vaccine. The use of recombinant NA (rNA) proteins expressed in yeast or insect cells elicits protection against lethal virus challenges in immunized mice. Ferrets immunized with rNA proteins exhibit a distinctive type of protection in addition to that provided by HA immunization alone. NA-inhibiting (NI) antibodies are known to limit virus spreading and to mitigate clinical symptoms of IAV infection. Mice immunized with a reverse-genetic reassortant H1N1 virus containing seasonal influenza virus NA exhibit cross-reactive NI antibodies and reduced mortality from pH1N1 virus challenges. Live attenuated influenza vaccines (LAIVs) for seasonal H1N1, H3N2 and pH1N1 strains have been reported as inducing cross-reactive NI antibodies to H5N1 viruses in ferrets, and NI antibodies elicited by a seasonal trivalent influenza vaccine have been reported as providing cross-protective immunity against lethal H5N1 challenges, also in ferrets. Further, NA-based virus-like particles (VLPs) containing NA, M1 and M2 have been shown to elicit more potent NI antibodies and to confer cross-protective immunity against H5N1 and pH1N1 viral challenges in mice. NI antibodies have also been detected in humans vaccinated with an H5N1 inactivated vaccine, as well as in humans exposed to natural infections. NA immunogenicity and cross-protective mechanisms remain unclear.